Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light and electron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.